Design, synthesis and biological evaluation of 2-mercapto-3-phenethylquinazoline bearing anilide fragments as potential antitumor agents: Molecular docking study

A novel series of 2-(3-phenethyl-4(3H)quinazolin-2-ylthio)-N-substituted anilide and substituted phenyl 2-(3-phenethyl-4(3H) quinazolin-2-ylthio) acetate were designed, synthesized and evaluated for their in-vitro antitumor activity. Compound 15 possessed remarkable broad-spectrum antitumor activity which almost sevenfold more active than the known drug 5-FU with GI(50) values of 3.16 and 22.60 mu M, respectively. Compound 15 exhibited remarkable growth inhibitory activity pattern against renal cancer (GI(50) = 1.77 mu M), colon cancer (GI(50) = 2.02 mu M), non-small cell lung cancer (GI(50) = 2.04 mu M), breast cancer (GI(50) = 2.77 mu M), ovarian cancer (GI(50) = 2.55 mu M) and melanoma cancer (GI(50) = 3.30 mu M). Docking study was performed for compound 15 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib. (c) 2013 Elsevier Ltd. All rights reserved.